HIV SeropositivityPhase 4OBERALNCT03374358

Effect on Liver Fat and Metabolic Parameters When Switching a Protease Inhibitor or Efavirenz to Raltegravir

A Phase 4 study testing Raltegravir in people with HIV Seropositivity and Metabolic Syndrome, run by Helsinki University Central Hospital at 1 site in Finland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study will provide data on the switch from a protease inhibitor or efavirenz to the new formulation of raltegravir (RAL) dosed once daily. The study group consists of patients with metabolic risk factors and co-morbidities, in need of optimization of their current ART to minimize the drug-related metabolic side… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV Seropositivity, Metabolic Syndrome, Fatty Liver
What is being tested?: Raltegravir
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 45 participants
Where: 1 siteFinland
Study dates: 10 Jan 2018to 30 Nov 2019
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Written informed consent (IC) obtained.
HIV-positive adult (age over 18) subjects currently on stable ART, with no changes in the ART regimens during the past 6 months.
Current ART includes either a protease inhibitor or efavirenz.
No documented or suspected resistance to integrase inhibitors or to NRTIs.
No prior history of virologic failure. Failure is defined as a confirmed plasma viral load > 200 cop/ml measured no less than six months after initiation or modification of therapy.
Virological blips accepted only if a single viral load measurement has been between 50-200 cop/ml followed by viral load < 50 cop/ml without the need to initiate a change in ART and no blip within 12 month window period prior to screening.

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Documented evidence of at least two HIV viral load < 50 cop/ml measurements during the past 12 months prior to inclusion: one within 6 months prior to screening.
HIV viral load < 50 cop/ml at screening.
BMI>25 kg/m2 and one metabolic syndrome condition, which are
BP ≥ 130/≥ 85 mmHg or hypertension medication currently in use or
fasting glucose ≥ 5.6 mmol/l or B-HbA1C > 42 mmol/mol or diabetes medication currently in use or
HDL < 1.0 mmol/l in men and < 1.3 mmol/l in women or triglycerides ≥ 1.7 mmol/l or a cholesterol-lowering regimen currently in use or
waist circumference > 94 cm in men and >80 cm in women (or respective cut off values for non-European ethnic groups as defined by International Diabetes Federation). OR
ultrasound or biopsy proven hepatosteatosis.

Who cannot join

Within 12 month window period prior to screening, HIV viral load measurement of >50 cop/ml.
More than one consecutive HIV viral load measurements of > 50 cop/ml in the treatment history after initial viral suppression with ART.
Chronic hepatitis B or C.
Daily alcohol consumption ≥ 30 g for men and ≥ 20 g for women.
Pregnancy or planned pregnancy during the study period.
Lipid or glucose lowering regimen or hormonal supplement started within 3 months before the planned study start.

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Psychiatric disorder, which prevents a study subject to understand the study protocol.
Other serious disease, which prevents a study subject to participate in the study.
For MRI/spectroscopy imaging: metal objects in the body or claustrophobia.

Trial locations and contacts

1 site in 1 country.

Finland1 site

Aurora hospital, Department of Infectious Diseases
Helsinki

Other trials in Finland

About this study

Official title: Effect on Liver Fat, Adipose Tissue and Metabolic Parameters When Switching a Protease Inhibitor or Efavirenz to Once Daily Raltegravir in HIV+ Patients With Body Mass Index Over 25 kg/m2 and With at Least One Metabolic Syndrome Component

The primary objective of this study is to investigate whether switching a protease inhibitor (PI) or efavirenz to raltegravir once daily reduces liver fat in patients who are overweight or obese and have at least one metabolic syndrome component. For this purpose, the liver fat content will be analyzed using the proton magnetic resonance spectroscopy.

In addition, the aim is to clarify the change in the body composition and metabolism in this study group. For this purpose the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes will be measured and subcutaneous tissue samples will be collected for future analyses of adipose tissue function.

Read the detailed description

The prevalences of overweight (body-mass-index, BMI 25-30 kg/m2) and obesity (BMI>30 kg/m2) are steadily increasing among HIV-infected patients globally. In parallel, the risk of non-alcoholic fatty liver disease (NAFLD) increases. Clinically alarming are the data which suggest that HIV infected have higher rates of progressive form of NAFLD than non-HIV infected age, gender and BMI matched controls.

As the treatment for HIV is life-long, it is crucial to understand the effects of different antiretroviral therapy (ART) regimens on metabolism. Some antiretroviral agents appear to promote unfavourable changes in metabolism (e.g. in blood lipids) and predispose to trunk fat redistribution and liver fat accumulation.

Raltegravir has been demonstrated to have beneficial impact on some metabolic parameters compared to the protease inhibitor class or efavirenz. In this study, the aim is to investigate whether switching a protease inhibitor or efavirenz to raltegravir reduces liver fat in patients who are overweight or obese and have at least one metabolic syndrome component. For this purpose, the proton magnetic resonance spectroscopy will be used.

In addition, the aim is to clarify the change in the body composition in this study group. For this purpose, the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes will be measured using MRI.

To acquire more knowledge on metabolic effects in adipose tissue level, subcutaneous adipose tissue biopsies will be collected together with blood, saliva and feces samples.

Conditions: HIV Seropositivity, Metabolic Syndrome, Fatty Liver
Being tested: Raltegravir
Medical subject headings: HIV Seropositivity, Metabolic Syndrome, Fatty Liver

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RaltegravirDrug
Also called Isentress
The aim of this study is to investigate whether switching a protease inhibitor (PI) or efavirenz to raltegravir has effect on liver fat and metabolism in HIV-infected patients who are overweight or obese and have at least one metabolic syndrome component .

Study groups in NCT03374358
Study group	Role	What they receive
No intervention arm.	No intervention	Study subjects will continue their current antiretroviral regimens, which include a protease inhibitor or efavirenz plus two nucleoside analog reverse-transcriptase inhibitors (NRTIs).
Raltegravir arm.	Experimental	Study subjects will switch their protease inhibitor or efavirenz to once daily raltegravir plus continue current nucleoside analog reverse-transcriptase inhibitors (NRTIs). Receives: Drug: Raltegravir

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Liver Fat
24 week value minus baseline value, liver fat % measured by proton magnetic resonance spectroscopy.
Measured: Baseline and 24 weeks

Secondary outcomes (2)

Change in Subcutaneous and Visceral Adipose Tissue Volume
24 week value minus baseline value: change in subcutaneous (SAT) and visceral (VAT) adipose tissue volume (mL) measured by magnetic resonance imaging. Analysis included a series of T1-weighted trans-axial images from 8 cm above to 8 cm below the 4th and 5th lumbar intervertebral disc (16 slices, field of view 375 x 500 mm2, slice thickness 10 mm).
Measured: Baseline and 24 weeks
Change in Body Weight and Total Body Fat
24 week value minus baseline value, change in body weight (kg) and total body fat (kg) measured by Bioelectrical Impedance Analysis.
Measured: Baseline and 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Jan 201830 Nov 2019

First posted15 Dec 2017
Study start10 Jan 2018
Primary completion2 Nov 2019
Study completion30 Nov 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for HIV SeropositivityStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: This study is a randomized, open, parallel design study.
Masking: None (open label)
Enrolment: 45 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03374358
Sponsor's protocol ID: OBERAL
Acronym: OBERAL
Status last verified: Aug 2021
First submitted: 2 Dec 2017
Last updated: 5 Sep 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Hanttu AM, Pekkala S, Satokari R, Hartikainen AK, Arkkila P, Pietilainen KH, Sutinen JP. Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study. AIDS. 2023 Feb 1;37(2):323-332. doi: 10.1097/QAD.0000000000003419. Epub 2022 Nov 10.
PubMed 36541643
Hanttu A, Vuoti S, Kivela P, Arkkila P, Lundbom N, Hakkarainen A, Lundbom J, Lehtimaki T, Viskari H, Lehtinen V, Pietilainen KH, Sutinen J. Liver Fat, Adipose Tissue, and Body Composition Changes After Switching from a Protease Inhibitor or Efavirenz to Raltegravir. AIDS Patient Care STDS. 2021 Sep;35(9):335-341. doi: 10.1089/apc.2021.0106.
PubMed 34524919

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All HIV Seropositivity trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effect on Liver Fat, Adipose Tissue and Metabolic Parameters When Switching a Protease Inhibitor or Efavirenz to Once Daily Raltegravir in HIV+ Patients With Body Mass Index Over 25 kg/m2 and With at Least One Metabolic Syndrome Component
ClinicalTrials.gov ID: NCT03374358
Acronym / sponsor ID: OBERAL / OBERAL
Conditions: HIV Seropositivity, Metabolic Syndrome, Fatty Liver
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 45 participants (actual)
Lead sponsor: Helsinki University Central HospitalUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: 10 Jan 2018 (actual)
Primary completion: 2 Nov 2019 (actual)
Study completion: 30 Nov 2019 (actual)
First posted: 15 Dec 2017 (actual)
Results: Posted 7 Jul 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

To acquire more knowledge on metabolic effects in adipose tissue level, subcutaneous adipose tissue biopsies will be collected together with blood, saliva and feces samples.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: This study is a randomized, open, parallel design study.

Arm	Type	Receives
No intervention arm.	No intervention	–Study subjects will continue their current antiretroviral regimens, which include a protease inhibitor or efavirenz plus two nucleoside analog reverse-transcriptase inhibitors (NRTIs).
Raltegravir arm.	Experimental	Drug: RaltegravirStudy subjects will switch their protease inhibitor or efavirenz to once daily raltegravir plus continue current nucleoside analog reverse-transcriptase inhibitors (NRTIs).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Written informed consent (IC) obtained.
HIV-positive adult (age over 18) subjects currently on stable ART, with no changes in the ART regimens during the past 6 months.
Current ART includes either a protease inhibitor or efavirenz.
No documented or suspected resistance to integrase inhibitors or to NRTIs.
No prior history of virologic failure. Failure is defined as a confirmed plasma viral load > 200 cop/ml measured no less than six months after initiation or modification of therapy.

Key exclusion criteria (9 listed)

Within 12 month window period prior to screening, HIV viral load measurement of >50 cop/ml.
More than one consecutive HIV viral load measurements of > 50 cop/ml in the treatment history after initial viral suppression with ART.
Chronic hepatitis B or C.
Daily alcohol consumption ≥ 30 g for men and ≥ 20 g for women.
Pregnancy or planned pregnancy during the study period.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RaltegravirAlso: IsentressThe aim of this study is to investigate whether switching a protease inhibitor (PI) or efavirenz to raltegravir has effect on liver fat and metabolism in HIV-infected patients who are overweight or obese and have at least one metabolic syndrome component .	Drug	Raltegravir arm.

Primary outcome

Change in Liver Fat
Time frame: Baseline and 24 weeks
24 week value minus baseline value, liver fat % measured by proton magnetic resonance spectroscopy.

2 secondary outcomes

Change in Subcutaneous and Visceral Adipose Tissue Volume
Time frame: Baseline and 24 weeks
Change in Body Weight and Total Body Fat
Time frame: Baseline and 24 weeks

Results and safety

Results posted to the registry on 7 Jul 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Control (= no Intervention Arm).	24	24
Raltegravir Arm.	21	19

Primary outcome: Change in Liver Fat

Time frame: Baseline and 24 weeks. Median (Inter-Quartile Range). Unit: % hepatic fat fraction

Measure	Control (= no Intervention Arm). n = 21	Raltegravir Arm. n = 18
Value	0.3 (-0.5 to 2.7)	0.6 (-0.3 to 1.6)

Population analysed: Only those participants with data available at the specified time points were analyzed.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Control (= no Intervention Arm).	1 of 24 (4.2%)	20 of 24 (83.3%)	0 of 24
Raltegravir Arm.	0 of 19 (0%)	16 of 19 (84.2%)	0 of 19

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36541643Hanttu AM, Pekkala S, Satokari R, Hartikainen AK, Arkkila P, Pietilainen KH, Sutinen JP. Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study. AIDS. 2023 Feb 1;37(2):323-332. doi: 10.1097/QAD.0000000000003419. Epub 2022 Nov 10.
Derived from this study: PubMed 34524919Hanttu A, Vuoti S, Kivela P, Arkkila P, Lundbom N, Hakkarainen A, Lundbom J, Lehtimaki T, Viskari H, Lehtinen V, Pietilainen KH, Sutinen J. Liver Fat, Adipose Tissue, and Body Composition Changes After Switching from a Protease Inhibitor or Efavirenz to Raltegravir. AIDS Patient Care STDS. 2021 Sep;35(9):335-341. doi: 10.1089/apc.2021.0106.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jussi Sutinen, MD PhD principal investigator

Helsinki University Central Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Raltegravir in people with HIV Seropositivity and Metabolic Syndrome, run by Helsinki University Central Hospital at 1 site in Finland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jul 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Liver Fat (time frame: Baseline and 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03374358, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Sep 2021.